This Phase I Small Business Innovative Research application proposes to develop a robust spectral domain optical coherence tomography (SDOCT) system suitable for combined diagnosis and treatment monitoring of osteoarthritis. Osteoarthritis is reaching epidemic proportions in the United States. Difficulty in diagnosing cartilage degeneration prior to the development of irreversible changes is a major obstacle to development and evaluation of disease modifying treatments for osteoarthritis. The earliest signs of degeneration occur prior to breakdown of the articular surface and include microstructural changes that are difficult to detect by radiographs, standard arthroscopy, or conventional magnetic resonance imaging (MRI). Orthopaedic surgeons perform over 650,000 arthroscopies a year for knee problems and find visible cartilage damage in up to 80% of patients. Professor Constance Chu, a subcontractor on this application, has shown that OCT can be used arthroscopically to nondestructively image articular cartilage at resolutions comparable to low power histology, and that OCT detectable changes found in the laboratory to indicate potentially reversible early cartilage insensitivity to anabolic growth factors were more prevalent in patients undergoing arthroscopic surgery for conditions associated with early degenerative joint disease. Because early chondrocyte metabolic incompetence has been implicated in the pathogenesis of osteoarthritis, these findings support the hypothesis that OCT can be used clinically to improve arthroscopic diagnosis of early articular cartilage degeneration. This proposal aims to develop novel clinical technology for arthroscopic OCT by developing new rigid borescope technology for sub-surface visualization of cartilage surfaces, synergizing the OCT probe with arthroscopic tools used for debridement, and reconfiguration/miniaturization of components to permit easy and frequent sterilization of the entire probe. [unreadable] [unreadable] [unreadable]